Accumulation of decarboxylated S-adenosyl-L-methionine in mammalian cells as a consequence of the inhibition of putrescine biosynthesis.
Biological transmethylation reactions and polyamine biosynthesis share the substrate S-adenosyl-L-methionine. Under normal conditions, decarboxylated S-adenosyl-L-methionine, the aminopropyl donor for polyamine biosynthesis, does not accumulate because of its rapid utilization in spermidine and spermine synthesis. Alteration of polyamine synthesis by DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of L-ornithine decarboxylase, leads to a striking accumulation of decarboxylated S-adenosyl-L-methionine in rat hepatoma cells cultured in vitro and in rat ventral prostate. This increase is due both to lack of putrescine and spermidine for the aminopropyltransferase reactions and to the elevation of S-adenosyl-L-methionine decarboxylase activity. The biological implications of accumulation of decarboxylated S-adenosyl-L-methionine are discussed with regard to the regulation of S-adenosyl-L-methionine decarboxylase activity and to the antiproliferative effects of DL-alpha-difluoromethylornithine.
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002478:Cells, Cultured; D000518:Eflornithine; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D008297:Male; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000494:pharmacology; D011467:Prostate / Q000201:enzymology; D011700:Putrescine / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009952:Ornithine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D011700:Putrescine; D000518:Eflornithine